Lactones, in particular gamma- and delta-lactones, are known to possess useful organoleptic properties and are important flavour and aroma constituents in many natural products. Gamma- and delta-lactones possess a chiral center and can occur in both enantiomeric forms. However, in nature the “R” chiral forms tend to be predominant (especially as the alkyl chain length increases). Naturally occurring gamma-lactones are found mainly in plants, whilst delta-lactones are found mainly in animals.
As a result of these properties, lactones have been employed as flavour and fragrance materials. These materials have a high flavour value due to their extremely low odour thresholds which average about 0.1 parts per million. For example, delta-decalactone, or 5-pentylpentanolide, (C10H18O2) has an odour detection threshold (in water) of 100 parts per billion, and occurs in products as diverse as Apricot, Blue Cheese, Burley Tobacco, Butter, Coconut, Mango, Peach, Raspberry, Rum, Strawberry and Tea.
In theory naturally occurring lactones may be isolated from plant material, for example, by extraction or distillation. However, in practice this is often impractical or impossible because the lactones are present in extremely low concentrations. Consequently, synthetic methods are often used to manufacture lactones for use as flavour and fragrance materials.
In using flavouring compounds, it has often been seen as important to be able to designate the flavouring compound as “natural”. As a result, research into synthetic methods of preparing flavouring compounds have tended to concentrate on obtaining the desired compound by physical, enzymatic or microbiological processes from a product of plant or animal origin, rather than from products derived from petrochemicals for example.
Thus, Cardillo et al., 1989, J. Org. Chem. 54, 4979-4980, have described the conversion of C14-C19 gamma-hydroxy alkene fatty acids into C8 and C11 delta-lactones and C9, C10 and C11 gamma-lactones in Cladiosporium suaveolens. The substrates are known to be present in nature, but there is no readily available source
U.S. Pat. No. 4,560,656 discloses the preparation of gamma-hydroxy-decanoic acid and subsequently of gamma-decalactone from castor oil or castor oil hydrolysate with specific microorganisms.
EP-A-0258993 discloses how to use ricinoleic acid as the substrate and other microorganisms are specified. However, the microorganisms mentioned are not generally recognised as “food grade”. Moreover, there is a need for processes that can produce higher quantities of lactones than those disclosed.
U.S. Pat. No. 5,215,901 discloses a process for producing delta-lactones on an industrial scale by using a micro-organism cultured in a culture medium containing a suitable substrate for producing delta-hydroxy-alkanoic acids. The micro-organism either does not metabolize delta-lactones, or only metabolises them very slowly. The micro-organism is cultured aerobically in a culture medium containing a hydroxy fatty acid having an odd number of carbon atoms between the carboxyl group and the carbon atom carrying the hydroxyl group. The micro-organism is cultured under such conditions and for a period of time sufficient to produce at least 0.1 g of delta-hydroxy-alkanoic acid per kg of fermentation broth. Then the delta-hydroxy-alkanoic acid is converted to the corresponding delta-lactone at a pH below 7. The delta-lactone is recovered substantially free from the original hydroxy fatty acid. The applicable micro-organisms are capable of effecting beta-oxidation of the hydroxy fatty acids used as starting materials. Examples of such micro-organisms may be bacteria, yeasts or filamentous fungi.
Purely chemical synthetic routes to produce lactones are also known. For example, a hydroxycarboxylic acid, Ia, which contains both an alcohol and a carboxylic acid functional group, can undergo an acid catalysed intramolecular esterification to produce a lactone, IIa. This lactonization process is an equilibrium reaction that is favoured if the lactone formed has a five- or six-membered ring. Lactones containing larger ring sizes may be produced by for example, removing the water produced in the reaction so as to move the unfavourable equilibrium towards the lactone.

Many gamma- and delta-lactones are formed so readily from the hydroxycarboxylic acids that it is not even necessary to add acid to catalyse the intramolecular esterification reaction.
EP-A-0176370 discloses the production of lactones, such as IIb, by reacting an unsaturated alcohol, such as IIIa, with carbon monoxide in the presence of a protonic acid and a catalyst comprising (a) at least one of the metals palladium, rhodium, ruthenium, iridium and cobalt, and (b) at least one of the metals copper, molybdenum and iron with (a) and (b) being in the form of either the elemental metal or a compound thereof. This process produced gamma- and delta-lactones in moderate to good yields, 15-80%.

Thus, there is a continuing need for improved processes for producing lactones.